Our research program focuses on four subject areas: [1] drug resistance of malaria parasites and the factors that affect clinical outcomes after antimalarial treatment; [2] the means by which malaria parasites avoid human immune defenses; [3] why strains of the most deadly malaria parasite (Plasmodium falciparum) show different infectivities to the cells of humans and other primates; and [4] the nature of protection against malaria that is conferred to children by such hemoglobin mutations as HbC and HbS (sickle-cell). In each of these areas we seek research advances that can improve the knowledge of disease processes in malaria and thereby support the development of new antimalarial chemotherapies, diagnostic tools, and vaccines. The research activities in our program are multidisciplinary and include field studies in malarious regions as well as programs of laboratory investigation on the NIH campus.